Regulation of the cell cycle is controlled by a family of cyclins, cyclin dependent kinases (CDKs), CDK regulatory kinases, and phosphatases. See, Lees, E., Curr. Opin. Cell. Biol. 1995, 7:773-780; Piwinica-Worms, H., J. Lab. Clin. Med. 1996, 128:350-354. Progression from the G2 phase to the M phase of the cell cycle requires the activityof cdc25 phosphatase. In Drosophila, mutations in the pelota gene have the same phenotype as mutations in the twine and/or string genes, which are cdc25 homologs, Eberhart, C. G. and Wasserman. S. A., Devel. 1995, 121:3477-3486. Specific cell cycle effects of pelota mutations are seen in both meiosis and mitosis, including G2/M arrest between mitotic and meiotic cell division, and disruption of nuclear envelope breakdown and spindle formation. Regulation of pelota offers a means of controlling a critical event in the cell cycle.
This indicates that the Pelota family has an established, proven history as therapeutic targets.
Clearly there is a need for identification and characterization of further members of Pelota family which can play a role in preventing, ameliorating or correcting dysfunctions or diseases, including, but not limited to, proliferative diseases such as leukemias, solid tumor cancers and metastases; chronic inflammatory proliferative diseases such as psoriasis and rheumatoid arthritis; proliferative cardiovascular diseases such as restenosis; prolifertive ocular disorders such as diabetic retinopathy; and benign hyperproliferative diseases such as hemangiomas.